登革热病毒患者的新蝶呤水平和犬/色氨酸比值显著升高，随后在康复后降低。

Neopterin levels and Kyn/Trp ratios were significantly increased in dengue virus patients and subsequently decreased after recovery.

机构信息

Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria.

SeraDiaLogistics, Munich, Germany.

出版信息

Int J Infect Dis. 2020 Feb;91:162-168. doi: 10.1016/j.ijid.2019.12.005. Epub 2019 Dec 9.

DOI:10.1016/j.ijid.2019.12.005

PMID:31821895

Abstract

OBJECTIVES

During dengue fever, a pronounced gamma-interferon immune response produces neopterin and promotes tryptophan degradation by the enzyme indoleamine-2,3-dioxygenase 1 (IDO-1). Activated IDO-1 is indicated by an increased kynurenine to tryptophan ratio (Kyn/Trp) in patients.

METHODS

Plasma levels of neopterin, kynurenine, and tryptophan were measured in 72 hospitalized dengue virus (DENV) patients and 100 healthy individuals. Plasma levels of neopterin, kynurenine, and tryptophan were also measured prospectively in a second cohort of 13 DENV patients; on the day of hospitalization, on day 2-3 at discharge, and 7-10 days after discharge. DENV RNA positivity was determined by qualitative and quantitative methodologies.

RESULTS

DENV RNA-positive patients presented significantly higher levels of neopterin (mean 36.5nmol/l) and Kyn/Trp ratios (mean 102μmol/mmol) compared to DENV RNA-negative individuals. A significant correlation between neopterin levels and Kyn/Trp ratios was observed in both DENV RNA-positive (Spearman's rho=0.37, p< 0.01) and DENV RNA-negative (Spearman's rho=0.89, p<0.001) patients. Kyn/Trp ratios were negatively correlated with platelet counts (Spearman's rho=-0.43, p<0.01) and positively correlated with liver enzymes: AST (Spearman's rho=0.68, p<0.01) and ALT (Spearman's rho=0.51, p<0.05). In addition, the follow-up data presented a significant decrease in neopterin levels and Kyn/Trp ratios within 10 days after hospital entry.

CONCLUSIONS

Neopterin levels and Kyn/Trp ratios were significantly increased in DENV patients and subsequently decreased after recovery.

摘要

目的

登革热期间，强烈的γ干扰素免疫反应产生新蝶呤，并通过酶吲哚胺 2,3-双加氧酶 1（IDO-1）促进色氨酸降解。活化的 IDO-1 表现为患者中犬尿氨酸与色氨酸比值（Kyn/Trp）增加。

方法

测量 72 例住院登革病毒（DENV）患者和 100 例健康个体的血浆中新蝶呤、犬尿氨酸和色氨酸水平。还前瞻性测量了第二批 13 例 DENV 患者的血浆新蝶呤、犬尿氨酸和色氨酸水平；在入院当天、出院时的第 2-3 天以及出院后 7-10 天。通过定性和定量方法确定 DENV RNA 阳性。

结果

与 DENV RNA 阴性个体相比，DENV RNA 阳性患者的新蝶呤（平均 36.5nmol/L）和 Kyn/Trp 比值（平均 102μmol/mmol）明显更高。在 DENV RNA 阳性（Spearman's rho=0.37，p<0.01）和 DENV RNA 阴性患者（Spearman's rho=0.89，p<0.001）中均观察到新蝶呤水平与 Kyn/Trp 比值之间存在显著相关性。Kyn/Trp 比值与血小板计数呈负相关（Spearman's rho=-0.43，p<0.01），与肝酶呈正相关：AST（Spearman's rho=0.68，p<0.01）和 ALT（Spearman's rho=0.51，p<0.05）。此外，随访数据显示，入院后 10 天内新蝶呤水平和 Kyn/Trp 比值显著下降。